Background: Comprehensive management efforts to reduce asthma morbidity among children in urban areas with high levels of poverty and large minority populations have been inconclusive. The National Cooperative Inner-City Asthma Study (NCICAS) demonstrated improved symptom outcomes but did not evaluate cost-effectiveness in this population. Objective: We sought to examine the incremental cost-effect-iveness of a comprehensive social worker–based education program and environmental control in children with asthma stratified by baseline level of asthma control. Methods: We performed a prospective cost-effectiveness analysis alongside a randomized trial. A total of 1033 children and their families residing in 8 inner-city urban areas in the United States were enrolled in the NCICAS. Outcomes included symptom-free days, cost per symptom-free day gained, and annual costs of asthma morbidity compared by baseline symptom control, previous hospitalization, and previous unscheduled physician visits. Results: The NCICAS intervention significantly reduced asthma symptoms. First-year intervention costs were $245 higher for the intervention children compared with those receiving usual care. There were no additional intervention-related costs during the second year. When compared with usual care, the intervention improved outcomes at an average additional cost of $9.20 per symptom-free day gained (95% CI, −$12.56 to $55.29). The intervention was cost saving in 3 strata of children with increasing asthma severity. Conclusions: A multifaceted asthma intervention program reduced symptom days and was cost-effective for inner-city children with asthma. In children with more severe disease, the intervention was substantially more effective and reduced costs compared with that seen in control children. Organizations serving this population should consider this strategy as part of a comprehensive disease-management program for asthma. (J Allergy Clin Immunol 2002;110:576-81.)